Feng G S, Ouyang Y B, Hu D P, Shi Z Q, Gentz R, Ni J
Department of Biochemistry and Molecular Biology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis 46202-5121, USA. Gensheng-Feng@IUCC. IUPUI.EDU
J Biol Chem. 1996 May 24;271(21):12129-32. doi: 10.1074/jbc.271.21.12129.
A human cytoplasmic signaling protein has been cloned that possesses the same structural arrangement of SH3-SH2-SH3 domains as Grb2. This protein is designated Grap for Grb2-related adaptor protein. The single 2.3-kilobase (kb) grap transcript was expressed predominantly in thymus and spleen, while the ubiquitously expressed grb2 gene produced two mRNA species of 3.8 and 1.5 kb. Grap and Grb2 consist of 217 amino acids and share 59% amino acid sequence identity, with highest homology in the N-terminal SH3 domain. The GrapSH2 domain interacts with ligand-activated receptors for stem cell factor (c-kit) and erythropoietin (EpoR). Grap also forms a stable complex with the Bcr-Abl oncoprotein via its SH2 domain in K562 cells. Furthermore, Grap is associated with a Ras guanine nucleotide exchange factor mSos1, primarily through its N-terminal SH3 domain. These results show that a family of Grb2-like proteins exist and couple signals from receptor and cytoplasmic tyrosine kinases to the Ras signaling pathway.
已克隆出一种人类细胞质信号蛋白，其具有与Grb2相同的SH3-SH2-SH3结构域排列。这种蛋白质被命名为Grap，即Grb2相关衔接蛋白。单一的2.3千碱基（kb）的grap转录本主要在胸腺和脾脏中表达，而普遍表达的grb2基因产生3.8 kb和1.5 kb的两种mRNA。Grap和Grb2由217个氨基酸组成，氨基酸序列同一性为59%，在N端SH3结构域中同源性最高。Grap的SH2结构域与干细胞因子（c-kit）和促红细胞生成素（EpoR）的配体激活受体相互作用。在K562细胞中，Grap还通过其SH2结构域与Bcr-Abl癌蛋白形成稳定复合物。此外，Grap主要通过其N端SH3结构域与一种Ras鸟嘌呤核苷酸交换因子mSos1相关联。这些结果表明，存在一类Grb2样蛋白，它们将来自受体和细胞质酪氨酸激酶的信号与Ras信号通路偶联起来。
